Combining Azacitidine and Ruxolitinib for treating higher-risk MDS/MPN

Clinical Study of Azacitidine Combined With Ruxolitinib in the Treatment of Higher-risk Myelodysplastic Syndromes∕Myeloproliferative Neoplasms

This study is testing if combining two medications, Azacitidine and Ruxolitinib, can help people with higher-risk Myelodysplastic Syndromes or Myeloproliferative Neoplasms feel better and improve their health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Drugs / interventions: ruxolitinib, Lenzilumab, Cobimetinib
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT05817955 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and efficacy of Azacitidine combined with Ruxolitinib in patients with higher-risk Myelodysplastic Syndromes/Myeloproliferative Neoplasms (MDS/MPN). It is an open-label, multi-centered study that aims to provide a new treatment option for patients who are not suitable for hematopoietic stem cell transplantation. The trial focuses on patients diagnosed with specific subtypes of MDS/MPN, particularly Chronic Myelomonocytic Leukemia (CMML) and others, based on clinical and morphological characteristics. The study will assess the treatment's effectiveness in improving patient outcomes and reducing the risk of disease progression.

Who should consider this trial

Good fit: Ideal candidates for this study are patients diagnosed with higher-risk MDS/MPN who are not suitable for hematopoietic stem cell transplantation.

Not a fit: Patients with lower-risk MDS/MPN or those who are suitable for hematopoietic stem cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with higher-risk MDS/MPN, potentially improving survival rates and quality of life.

How similar studies have performed: While there have been studies on individual treatments for MDS/MPN, the combination of Azacitidine and Ruxolitinib in this context is relatively novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

• According to WHO (2016) classification, researchers made the diagnosis of CMML based on clinical and morphological characteristics. Other criteria should be met: 1) Neut ≥2x109/L, PLT ≥25x109/L, 2) belongs to the following prognostic risk group according to CPSS-MOL or MMM : CPSS-MOL: inter-2 risk (2 to 3 points); high risk (≥4 points);

MMM: inter-2 risk (2.5 to 4.5 points); high risk (≥5 points), or:

* According to the WHO (2016) classification standards (Arber 2016), researchers made the diagnosis of other types of MDS/MPN (including aCML and MDS /MPN-U) based on clinical and morphological characteristics. Other criteria should be met: 1) Neut ≥2x109/L, PLT ≥25x109/L, 2) Bone marrow blasts ≥5%;
* Patients who are not suitable for hematopoietic stem cell transplantation (HSCT) according to the local medical standards and treatment guidelines;
* Patients who are suitable for Azacitidine(AZA) treatment according to the local medical standards and treatment guidelines;
* BCR-ABL positive Chronic Myelogenous Leukemia (CML) and Ph chromosomal negative classic myeloproliferative Neoplasms, such as essential thrombocytosis (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) are excluded;
* Age is between 18 to 80 years old;
* ALT, AST and serum bilirubin is no more than 2 times of the upper limit of normal values (ULN), serum creatinine is no more than 150 μmol/L, and serum myocardial enzyme is less than (the same age) 2 times of normal value upper limit;
* The LVEF determined by the echocardiography is no less than 50%;
* Estimated glomerular filtration rate (EGFR) is no less than 30ml · min · 1.73m2;
* Eastern Tumor Collaboration Group (ECOG) physical states score is 0 to 2;
* Informed Consent Form is signed by patients or legal agents.

Exclusion Criteria:

* BCR-ABL positive Chronic Myelogenous Leukemia (CML) and Ph chromosomal negative classic myeloproliferative Neoplasms, such as essential thrombocytosis (ET), polycythemia vera (PV) and primary myelofibrosis (PMF) ;
* Low risk or inter-1 risk CMML patients according to CPSS-MOL or MMM scores; other types of MDS/MPN with less than 5% bone marrow blasts;
* Patients with Neut\<2x109/L, PLT\<25x109/L;
* Secondary acute leukemia, myeloid sarcoma, and blast phase of aCML;
* Patients who are allergic to any drug involved in the trial;
* Pregnancy, lactating Women, and patients who are unwilling to use contraceptives;
* Patients with abnormal Liver and kidney function which exceeded the inclusion criteria;
* Patients with organic heart disease with clinical symptoms or heart dysfunction (NYHA ≥ level 2);
* Patients with other malignancies at the same time except the following situations:

Patients had received treatment for the purpose of cure and had no active malignancies for at least 5 years prior to enrollment; 2)Patients had received sufficient treatment, non-melanoma skin cancer or malignant freckles -like moles with no signs of illness (even if random grouping is less than 3 years); 3)Received sufficient treatment, in situ cancer without signs of illness (even if the random group is less than 3 years);

* Patients with AIDS, syphilis, active hepatitis B (HBV-DNA can be measured) and hepatitis C;
* Patients with cardiovascular diseases with clinical significance, such as arrhythmia that have not been controlled or have symptoms, congestive heart failure or myocardial infarction within 6 months, or level 3 (moderate) or level 4 (Severe) heart disease (NYHA according to the New York Heart Society's functional grading method);
* Patients with any situations that might interfere with research procedures or results, or have the medical status or disease that will bring a certain risk to participating in this study judged by researchers (such as activity systemic infection);
* Patients who can't understand or follow the research plan;
* Patients who are under 18 or over 80 years old;
* Patients who underwent a major surgery within 4 weeks before the random grouping;
* Patients who are participating in other clinical trials one month before joining the group;
* Patients who rely on illegal drugs;
* Patients with psychological disorders or cognitive disorders

Where this trial is running

Nanjing, Jiangsu

• The First Affiliated Hospital of Nanjing Medical University — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Zhongxun Shi, MD

Conditions MDS/MPN